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An inorganic film of ruthenium hexachlororuthenate (RuRu[Cl.sub.6]), deposited on the surface of a glassy carbon electrode, exhibits electrocatalytic activity in the oxidation of purine nucleosides, such as guanosine and adenosine. Appropriate operating conditions are found for fabricating a polymer film on the surface of glassy carbon and for recording the maximum electrocatalytic current for the modified electrode. A method for the selective voltammetric determination of guanosine and adenosine in their simultaneous presence at an electrode modified by a RuRu[Cl.sub.6] film is developed. A procedure is proposed for the amperometric detection of purine nucleosides with this modified electrode under the conditions of flow-injection analysis. The linear dependence of the analytical signal on the concentration of guanosine and adenosine is observed up to 5 x [10.sup.-6] M in the stationary mode and up to 5 x [10.sup.-7] M in the flow system. The proposed method for the selective determination of guanosine and adenosine was tested in the analysis of human urine. Keywords: chemically modified electrodes, inorganic polymer films, ruthenium hexachlororuthenate, guanosine, adenosine, electrocatalysis, electroanalysis, flow-injection analysis, Purine bases associated with deoxyribose through an [alpha]-glycosidic bond belong to the class of purine nucleosides known for their metabolic and biological properties. Purine nucleosides, guanosine and adenosine, which are [...]

An ab initio calculation results for the interaction of 2'deoxyguanosine monophosphate with the hydrated [Mg.sup.2} cation is presented. The studies provide insight into significant influence of the presence of hydrated [Mg.sup.2} on formation of several hydrogen bonds between hydrated [Mg.sup.2} and guanine and also on pyramidalization of the amino group.

A study was conducted to understand the kinetics of redox reactions of the [Pt.sup.4](IV) complexes trans-Pt(d,l)(1,2-[(N[H.sub.2]).sub.2][C.sub.6][H.sub.10])[Cl.sub.4] ([Pt.sup.IV][Cl.sub.4](dach)]) and Pt(N[H.sub.2]C[H.sub.2]C[H.sub.2]N[H.sub.2])[Cl.sub.4] (Pt.sup.IV][Cl.sub.4](en)]) with 5'- and 3' -dGMP. The findings reveal that 5'-hydroxo has less rotational barrier than 5'-phosphate, but it is geometrically unfavorable for internal electron transfer.

A study is presented to demonstrate that two tautomers of one-electron-oxidized guanine are produced by the protonation of an 8-haloguanine electron adduct. The reaction of hydrated electrons [e.sub.aq.sup.-] with 8-haloguanosine or 8-halo-2'-deoxyguanosine produces the first observable transient species that decay unimolecularly to give the one-electron oxidized guanosine or 2'deoxyguanosine.

The result of photocross-linking analysis of native and minimal hammerheads containing photoreactive nucleobases, introduced at specific sites within catalytic core is described. The results obtained support a model in which both hammerheads partition between 2-folds, an inactive ground state similar to the crystallographic structures and an active fold characterized by interactions between putative catalytic nucleobases G8 and G12 and the substrate cleavage site.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2006.02.003 Byline: Stephen P.L. Cary (1), Jonathan A. Winger (2), Emily R. Derbyshire (3), Michael A. Marletta (1)(3)(4) Abstract: Nitric oxide (NO) triggers various physiological responses in numerous tissues by binding and activating soluble guanylate cyclase (sGC) to produce the second messenger cGMP. In vivo, basal NO/cGMP signaling maintains a resting state in target cells (for example, resting tone in smooth muscle), but an acute burst of NO/cGMP signaling triggers rapid responses (such as smooth muscle relaxation). Recent studies have shown that the sGC heterodimer comprises at least four modular domains per subunit. The N-terminal heme domain is a member of the H-NOX family of domains that bind O.sub.2 and/or NO and are conserved in prokaryotes and higher eukaryotes. Studies of these domains have uncovered the molecular basis for ligand discrimination by sGC. Other work has identified two temporally distinct states of sGC activation by NO: formation of a stable NO-heme complex results in a low-activity species, and additional NO produces a transient fully active enzyme. Nucleotides also allosterically modulate the duration and intensity of enzyme activity. Together, these studies suggest a biochemical basis for the two distinct types of NO/cGMP signal observed in vivo. Author Affiliation: (a) Department of Chemistry (b) Howard Hughes Medical Institute (c) Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA (d) Division of Physical Biosciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

The interstrand N(super 2), N(super 2)-dG DNA cross-linking chemistry of the acrolein-derived gamma-OH-1,N(super 2) propandeoxyguanosine (gamma-OH-PdG) adduct in the 5'-CpG-3' sequences is monitored within a dodecamer duplex by NMR spectroscopy. When the gamma-OH-PdG adduct contained within the 5'-CpG-3' sequence is annealed into the duplex DNA opposite T, a mixture of the 1,N(super 2)-dG cyclic adduct, the aldehyde, and the diol, but no cross-link, is observed.

The photooxidation of two kinetically fast electron hole traps N4-cyclopropyl-cytosine [(super CP)C] and N2-cyclopropylamine-guanosine [(super CP)G], incorporated in DNA duplexes of various sequence, is examined using different photooxidants. It is found that delocalized domains within the base pair stack form transiently based upon sequence-dependent DNA structure and dynamics, suggesting that DNA charge transport is remarkably sensitive to DNA sequence and structure.

A series of receptors designed to simultaneously bind the Watson-Crick and Hoogsteen sites of guanosine are synthesized, and their binding of guanosine tri-O-pentanoate is probed. The guanosine receptors are synthesized with aminonaphthalene or aminoquinoline auxiliary groups tethered to N-4 of cytosine through a methylene or carbonyl group.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.04.015 Byline: Mihaela Diaconu (1), Ute Kothe (3), Frank Schlunzen (4), Niels Fischer (2), Jorg M. Harms (4), Alexander G. Tonevitsky (5), Holger Stark (2), Marina V. Rodnina (3), Markus C. Wahl (1) Abstract: The L7/12 stalk of the large subunit of bacterial ribosomes encompasses protein L10 and multiple copies of L7/12. We present crystal structures of Thermotoga maritima L10 in complex with three L7/12 N-terminal-domain dimers, refine the structure of an archaeal L10E N-terminal domain on the 50S subunit, and identify these elements in cryo-electron-microscopic reconstructions of Escherichia coli ribosomes. The mobile C-terminal helix [alpha]8 of L10 carries three L7/12 dimers in T. maritima and two in E. coli, in concordance with the different length of helix [alpha]8 of L10 in these organisms. The stalk is organized into three elements (stalk base, L10 helix [alpha]8-L7/12 N-terminal-domain complex, and L7/12 C-terminal domains) linked by flexible connections. Highly mobile L7/12 C-terminal domains promote recruitment of translation factors to the ribosome and stimulate GTP hydrolysis by the ribosome bound factors through stabilization of their active GTPase conformation. Author Affiliation: (1) Rontgenkristallographie, Max-Planck-Institut fur Biophysikalische Chemie, Am FaAberg 11, D-37077 Gottingen, Germany (2) 3D Kryo-Elektronenmikroskopie, Max-Planck-Institut fur Biophysikalische Chemie, Am FaAberg 11, D-37077 Gottingen, Germany (3) Institute of Physical Biochemistry, University of Witten/Herdecke, Stockumer StraAe 10, D-58448 Witten, Germany (4) Max-Planck-Arbeitsgruppen fur Strukturelle Molekularbiologie, DESY, NotkestraAe 85, D-22607 Hamburg, Germany (5) Biological Department, MV Lomonosov Moscow State University, Vorobyevy Gory, Moscow 119899, Russia Article History: Received 30 November 2004; Revised 4 March 2005; Accepted 14 April 2005 Article Note: (miscellaneous) Published: June 30, 2005

The chemical viability of rG-to-aG formation through rG addition to a synthetic cyanoamine derivative is demonstrated. This establishes an alternative to the common hypothesis that assumes G-to-G cross-link formation occur by direct nucleophilic aromatic substitution of a guanosinediazonium ion by a guanosine.

Cyclic voltammetry was used to measure the rates of the chemical oxidation of guanine (G), guanosine (Gs), 2'-deoxyguanosine (dG), and 2'-deoxyguanosine 5'-monophosphate (dGMP) by electrochemically generated tris(2,2'-bipyridyl)ruthenium(III). The numeric fit of voltammograms to an ECCCE type of mechanism provided the equilibrium and rate constants of the two-step chemical oxidation of the guanine species.

The synthesis of the oxetane-A and oxetane-G nuclesides and their incorporations into antisense oligonucleotides(AONs) and their structural and antisensence properties are compared with those of the T and C modified AONs.Oxetane-A and -G modified AONs showed their target affinity with complimentary RNA, and the thermodynamic parameters to be identical or very close to the native AON/RNA duplex.

Hydrolytic reactions of guanosyl-(3',3')-uridine and guanosyl-(3',3')-(2',5'-di-O-methyluridine) are described. The mechanisms of the partial reactions, in particular the effects of 2'-hydroxyl group on the departure of the 3'-linked nucleoside, are discussed.

The nitrosative deaminations (37 0C, NaNO2, NaAc buffer, pH 3.7) of guanosine 1r in (O(super 18))-water (97.65) and (6-O(super 18))-1r in normal water are studied. The results show that oxanosine is formed via 5-cyanoimino-4-oxomethylene-4, 5-dihydromidazole, 5, and its 1,4-addition product 5-cyanoamino-4-imidazolecarboxyllic acid, 6.

The cooperative effect of solvophobic interactions and hydrogen bonding is exploited to self-assemble supramolecular helical architectures of 8-oxoguanosines in different environments. The self-assembly into helical structures is completely different from that of the parent guanosines which, in the same experimental conditions, form flat, ribbonlike structures.

The relative affinity of monovalent cations for stacking G-quartet structure formed by guanosine 5'monophospahe (5'-GMP) self-association at pH8 is examined by conducting a solid-state multinuclear ((super 23)Na, (super 15)N, (super 13)C and (super 31)P) NMR study. Results show the direct determination of the thermodynamic parameters for competitive binding between Na(super +) and M(super +) ions to two different sites of the 5'-GMP structure.

ADARs are adenosine deaminases that act on RNA and are responsible for RNA-editing reactions that occur in eukaryotic mRNAs, including the mRNAs of glutamate and serotonin receptors. ADARs that are capable of editing biologically relevant RNA substrates are identified and 8-Aza substitution at adenosine in various RNA substrates accelerates the rate of deamination at these sites by ADAR2 (2.8-17-fold).

ESIMS, X-ray crystallography, and NMR spectroscopy are used to study the anion's influence on the structure and dynamics of self-assembled ion pair receptors formed from guanosine G. The structure and electronics of the organic anions, bound to the assembly's periphery are crucial for controlling the kinetic stability of these cation-filled G-quadruplexes.

The inter- and intramolecular quenching efficiency of DNA nucleotides with rhodamine and oxazine derivatives in aqueous solution is studied. The results show that similar to the aggregation tendency of organic dyes, oxazine and rhodamine dyes tend to aggregate with DNA nucleotides in aqueous surroundings.

(super 13)C and (super 15)N chemical shift tensor principal values along with the orientations of the principal tenor components inside a particular molecular framework are sensitive to electronic structure and intermolecular reactions. (super 13)C and (super 15)N chemical shift tensor principal values for adenosine, guanosine dihydrate, 2'-deoxythymidine as well as cytidine are measured on natural samples, and effects of variations in certain embedded ion method parameters are studied.

Peroxymitrite reacts with 2',3',5'-tri-O-acetyl-guanosine to yield a novel compound identified as 1-(2,3,5-tri-O-acetyl-Beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6). This characterization was achieved using a combination of UV/vis spectroscopy and ESI-MS.

A systematic variation of reaction conditions that has led to an efficient, straightforward synthesis of 2'-C-beta-methylguanosine with high regio- and stereoselectivity is described. The strategy also improved regioselecitivity in the synthesis of guanosine and might provide a generally useful approach for the synthesis of other guanosine nucleosides by glucosylation.

New folding pathways are examined for human telomic type-1 and type-2 G-quadruplex conformations through intermediate hairpin and triplex structures. Stacking of G-tetrads with the same conformation is more stable than mixed stacking, which has indicated the formation of type-1 and type-2 G-quadruplex structures with the possibility of hairpin and triplex intermediates.

The first functional and structural characterization of the inosine-guanosine-specific nucleoside hydrolase (NH) from Trypanosoma brucei brucei is reported. The study identified nanomolar iminoribitol-based inhibitors which could be important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases.

The base pairing of 9-deaza-2' -deoxyguanosine (CdG) is examined by incorporating it into DNA and paired it with either dC or dA. The results have shown that CdG:dC base pairs are destabilized relative to dG:dC as a result of structural constraints imposed by the C-nucleotide character of CdG and CdG:dA base pairs are less stable than OdG:dA base pairs because of a third long-range interaction that is possible in OdG:dA but not in CdG:dA.

[N,1-[super 15][N.sub.2]]-Guanosine, or [1,N[H.sub.2]-[super 15][N.sub.2]]-guanosine and derivatives are prepared from tri-O-acetylinosine, through N-nitration and reaction with [super 15]N[H.sub.2]OH, which is followed by conversion of the [sper 15]N-labeled 1-hydroxyinosine to the corresponding 2,6-dichloropurine riboside. The sequential one-pot C-O and C-N key couplings of the dichloro derivative with PhC[H.sub.2]OH and PhCO[super 15]N[H.sub.2] or [super i]PrCO[super 15]N[H.sub.2] is obtained, with Pd(0)-Xantphos as the best choice of five different catalytic systems examined.

Oligo(p-phenylene-vinylene) oligomers capped with a guanosine or a guanine moiety are prepared via a palladium-catalyzed cross-coupling reaction and their self-assembly is studied in solution, solid state and on surfaces. The studies have shown that these [pi]-conjugated molecules self-associate in a mixture of hydrogen-bonded oligomers, among which the G-quartet structure is predominant if the steric hindrance around the guanine base is important.

The article presents a complete characterization of the structure of 1,[N.sup.2]-ethenodeoxyguanosine lesion (1,[N.sup.2]-[sigma]dG), which is shown to have no opposite dC. The biological processing of the discussed lesion is shown to be highly affected by the stabilization of the Dpo4 polymerase.

Oligonucleotides substituted with (R)- and (S)-CEdG and the corresponding triphosphates (R)- and (S)-CEdGTP (CEdG=[N.sup.2]-(1-carboxyethyl)-2'-deoxyguanosine) were synthesized to examine the miscoding potential in the adduct and base-pairing preferences for each stereoisomer. The results indicated that CEdG within template DNA and the corresponding triphosphate which possess different syn/anti conformations during replication influenced the base-pairing preferences.

Ultrafast UV-vibrational spectroscopy is used for examining how vibrational excitation of the bridge has changed photoinduced electron transfer between donor (dimethylaniline) and acceptor (anthracene) moieties bridged by a guanosine-cytidine base pair (PC). The studies have shown that the effect is linked to a dynamic modulation of the donor-acceptor coupling interaction by weakening of H-bonding and by disruption of the bridging base-pair planarity.

Steady-state [super 1]H photo-chemically induced dynamic nuclear polarization (CIDNP) experiments are conducted on deoxygenated aqueous solutions of [[Ru[(phen).sub.3]].sup.2+], [[Ru[(tap).sub.2](phen)].sup.2+], and [[Ru[(tap).sub.3]].sup.2+] (tap = 1,4,5,8-tetraazaphenanthrene, phen = 1,10-phenanthroline) in the presence of guanosine-5'-monophosphate or N-acetyltyrosine. The [super 1]H photo-CIDNP seen for the biomolecules is weak, however, up to 60% polarization enhancement is seen for H-2 and H-7 of the tap ligands, which has shown high unpaired electron density in the vicinity of these atoms in the transient radical pair.

An optimum balance between repulsive steric and attractive [pi]-[pi], dipole-dipole noncovalent interactions between subunits of a lipophilic 8-(3-pyridyl)-2'-deoxyguanosine derivative which facilitated the high fidelity formation of a stable and discrete self-assembled dodecamer is reported. The addition of dodecamers to a supramolecular construction toolbox containing octamers and hexadecamers made from other 8-aryl-2'-deoxyguanosine derivatives could be applied to prepare a wide variety of self-assembled nanostructures where the size and the number of functional elements could be precisely fine-tuned for specific applications.

The abasic lesion-induced energetic enhancement of slipped/looped structures which provides a linkage between base excision repair (BER) and DNA expansion is described. The impact of abasic-induced energetic alterations in the properties of regions proximal to and/or within triplet repeat domains on the BER machinery of repair and the potential modulation of levels of DNA expansion is also discussed.

The [super 18]O kinetic isotope effects (KIEs) in guanosine 5- triphosphate (GTP) hydrolysis catalyzed by Ras in the presence of [GAP.sup.334] or [NF1.sup.333], the catalytic fragment of p120GAP or NF1 are measured to understand the mechanisms of GTPase activation protein (GAP)-facilitated GTP hydrolysis reactions. The results indicated that the arginine finger of GAP and amide protons in the P-loop of Ras stabilized the negative charge on the [beta]-[gamma] bridge oxygen and the pro-S [beta] nonbridge oxygen of a loose transition state, while Lys-16 of Ras and [Mg.sup.2+] only contributed in substrate binding.

A supramolecular assembly containing an isoguanosine pentaplex with both a protein-binding face and a reporter face is generated. The supramolecular assembly is bound multivalently to the pentameric human C-reactive protein when phosphocholine is appended to the protein-binding face.

The use of silanes to react indiscriminately with RNA was explored to understand the primary factor governing reactivity which is solvent accessibility. This silane-based chemistry could find potential application as a direct and quantitative approach to probe solvent accessibility at the base pairing face of guanosine in RNA.

The reversible high fidelity switching between two discrete self-assembled supramolecules made from a lipophilic 8-phenyl-2'-deoxyguanosine derivative induced by an indirect solvent effect is described. The switching process has resulted from an unprecedented subtle interplay between the activity of potassium iodide and the steric crowding within the self-assembled structure.

Two approaches are described for preparing of 2'-C-[beta]-methyl-2'-deoxyguanosine via 2'-radical deoxygenation. First approach has started from 1,3,5-tri-O-benzoyl-[alpha]-D-ribofuranose and the second approach has started from guanosine.

The trans-4-hydroxynonenal (HNE)-derived diastereomeric (6S, 8S, 11S) and (6R, 8S, 11R) cyclic hemiacetals were examined to understand the structural differences of the HNE-derived exocyclic 1,[N.sup.2]-dG adduct. The stereochemical differences in orientation demonstrated the interchain cross-links in the 5'-Cpg-3' sequence formed by stereoisomer adducts (6S, 8R, 11S) and the (6S, 8S, 11R).

The syntheses of new blue luminescent [N.sup.2]-modified guanosine derivatives with chromophores p-4,4'-biphenyl-N[Ph.sub.2], p-4,4'-biphenyl-N[(2-py).sub.2], and p-4,4'-biphenyl-2-(2'-pyridyl)benzimidazolyl, are described. The anion-dependent circular dichroism (CD) response of the chromophores toward Zn(II) salt has shown the involvement of intramolecular hydrogen bonding between the acetate bound to the Zn(II) ion and the hydroxyl groups of the guanosine.